scholarly journals Antigen processing and presentation by glomerular visceral epithelium in vitro

1991 ◽  
Vol 39 (1) ◽  
pp. 71-78 ◽  
Author(s):  
Donna L. Mendrick ◽  
Dawn M. Kelly ◽  
Helmut G. Rennke
Keyword(s):  
Antigen Processing ◽  
Antigen Processing And Presentation ◽  
Visceral Epithelium

Phagosome-regulated mTOR Signalling during Sarcoidosis Granuloma Biogenesis

2020 ◽  
pp. 2002695 ◽  
Author(s):  
Elliott D. Crouser ◽  
Landon W. Locke ◽  
Mark W. Julian ◽  
Sabahattin Bicer ◽  
Wolfgang Sadee ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Antigen Processing ◽  
Mononuclear Cells ◽  
Latent Tuberculosis ◽  
Granuloma Formation ◽  
Molecular Characteristics ◽  
Immune Reactivity ◽  
Peripheral Blood Mononuclear ◽  
Antigen Processing And Presentation

IntroductionSarcoidosis and tuberculosis are granulomatous pulmonary diseases characterised by heightened immune reactivity to Mycobacterium tuberculosis (M.tb.) antigens. We hypothesised that an unsupervised analysis comparing the molecular characteristics of granulomas formed in response to M.tb. antigens in patients with sarcoidosis or latent tuberculosis infection (LTBI) would provide novel insights into the pathogenesis of sarcoidosis.MethodsA genomic analysis identified differentially expressed (DE) genes in granuloma-like cell aggregates formed by sarcoidosis (n=12) or LTBI patients (n=5) in an established in vitro human granuloma model wherein peripheral blood mononuclear cells (PBMCs) were exposed to M.tb. antigens (beads coated with purified protein derivative, PPD) and cultured for 7 days. Pathway analysis of DE genes identified canonical pathways, most notably antigen processing and presentation via phagolysosomes, as a prominent pathway in sarcoidosis granuloma formation. The phagolysosomal pathway promoted mTORc1/STAT3 signal transduction. Thus, granuloma formation and related immune mediators were evaluated in the absence or presence of various pre-treatments known to prevent phagolysosome formation (chloroquine) or phagosome acidification (bafilomycin A1) or directly inhibit mTORc1 activation (rapamycin).ResultsIn keeping with genomic analyses indicating enhanced phagolysosomal activation and predicted mTORc1 signalling, it was determined that sarcoidosis granuloma formation and related inflammatory mediator release was dependent upon phagolysosome assembly and acidification and mTORc1/S6/STAT3 signal transduction.ConclusionsSarcoidosis granulomas exhibit enhanced and sustained intracellular antigen processing and presentation capacities, and related phagolysosome assembly and acidification are required to support mTORc1 signalling to promote sarcoidosis granuloma formation.

scholarly journals Cellular Pathway(S) of Antigen Processing and Presentation in Fish APC: Endosomal Involvement and Cell-Free Antigen Presentation

1992 ◽  
Vol 3 (1) ◽  
pp. 51-65 ◽  
Author(s):  
Abbe N. Vallejo ◽  
Norman W. Miller ◽  
Nancy E. Harvey ◽  
Marvin A. Cuchens ◽  
Gregory W. Warr ◽  
...  
Keyword(s):  
Immune Responses ◽  
Channel Catfish ◽  
Antigen Processing ◽  
Current Data ◽  
Immune Functions ◽  
Protein Antigens ◽  
Blood Leukocytes ◽  
Lower Vertebrate ◽  
Antigen Processing And Presentation

Studies were conducted to address further the role(s) of antigen processing and presentation in the induction of immune responses in a phylogenetically lower vertebrate, specifically a teleost, the channel catfish. In particular, studies were aimed at determining the subcellular compartments involved in antigen degradation by channel catfish antigen-presenting cells (APC) as well as ascertaining the reexpression of immunogenic peptides on the surfaces of APC. The results showed that exogenous protein antigens were actively endocytosed by APC as detected by flow cytometry. Use of radiolabeled antigen and subcellular fractionation protocols also showed that antigen localized in endosomes/lysosomes. Furthermore, there was an apparent redistribution of antigen between these organelles and the plasma membrane during the course of antigen pulsing. Functional assays for the induction ofin vitroantigen-specific proliferation of immune catfish peripheral blood leukocytes (PBL) showed that membrane preparations from antigen-pulsed autologous APC were highly stimulatory. The magnitude of responses elicited with such membrane preparations was very similar to that of PBL cultures stimulated with native antigen-pulsed and fixed intact APC or prefixed intact APC incubated with a peptide fragment of the nominal antigen. Current data further corroborate our previous findings that steps akin to antigen processing and presentation are clearly important in the induction of immune responses in lower vertebrates like fish, in a manner similar to that seen in mammalian systems. Consequently, it would appear that many immune functions among the diverse taxa of vertebrates are remarkably conserved.

scholarly journals Inhibition of Antigen Presentation by the Glycine/Alanine Repeat Domain Is Not Conserved in Simian Homologues of Epstein-Barr Virus Nuclear Antigen 1

1999 ◽  
Vol 73 (9) ◽  
pp. 7381-7389 ◽  
Author(s):  
Neil W. Blake ◽  
Amir Moghaddam ◽  
Pasupuleti Rao ◽  
Amitinder Kaur ◽  
Rhona Glickman ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Antigen Processing ◽  
Epstein Barr Virus ◽  
Cytotoxic T Lymphocyte ◽  
Nuclear Antigen ◽  
Old World ◽  
Barr Virus ◽  
Epstein Barr ◽  
Antigen Processing And Presentation

ABSTRACT Most humans and Old World nonhuman primates are infected for life with Epstein-Barr virus (EBV) or closely related gammaherpesviruses in the same lymphocryptovirus (LCV) subgroup. Several potential strategies for immune evasion and persistence have been proposed based on studies of EBV infection in humans, but it has been difficult to test their actual contribution experimentally. Interest has focused on the EBV nuclear antigen 1 (EBNA1) because of its essential role in the maintenance and replication of the episomal viral genome in latently infected cells and because EBNA1 endogenously expressed in these cells is protected from presentation to the major histocompatibility complex class-I restricted cytotoxic T-lymphocyte (CTL) response through the action of an internal glycine-alanine repeat (GAR). Given the high degree of biologic conservation among LCVs which infect humans and Old World primates, we hypothesized that strategies essential for viral persistence would be well conserved among viruses of this subgroup. We show that the rhesus LCV EBNA1 shares sequence homology with the EBV and baboon LCV EBNA1 and that the rhesus LCV EBNA1 is a functional homologue for EBV EBNA1-dependent plasmid maintenance and replication. Interestingly, all three LCVs possess a GAR domain, but the baboon and rhesus LCV EBNA1 GARs fail to inhibit antigen processing and presentation as determined by using three different in vitro CTL assays. These studies suggest that inhibition of antigen processing and presentation by the EBNA1 GAR may not be an essential mechanism for persistent infection by all LCV and that other mechanisms may be important for immune evasion during LCV infection.

scholarly journals 914 Loss of LKB1 is associated with resistance to IFN-gamma and T cell killing in non-small cell lung cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A960-A960
Author(s):  
Alexandre Reuben ◽  
Peixin Jiang ◽  
Hui Nie ◽  
Ana Galan Cobo ◽  
Minghao Dang ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Cell Killing ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Ifn Gamma ◽  
Presentation Pathway ◽  
Antigen Processing And Presentation

BackgroundKRAS-mutant non-small cell lung cancers (NSCLC) have exhibited unique response patterns to immunotherapy based on their co-occurring mutations. Patients harboring KRAS & STK11/LKB1 co-mutations (KL) have experienced shorter progression-free and overall survival compared to those with only KRAS mutations (K). Despite their limited responses, KL tumors exhibit a tumor mutational burden comparable to their K counterparts, suggesting the presence of additional mechanisms impairing antigen-specific responses. Accordingly, here we investigated the role of the MHC I antigen processing and presentation pathway in KL tumors.MethodsTCGA lung adenocarcinoma (LUAD) data were investigated for changes in expression of HLA molecules and chaperones involved in antigen processing and presentation. In mice, we performed single cell RNA sequencing of resected LKR13 K and KL tumors to evaluate changes in the tumor microenvironment and intrinsic differences in tumor antigen processing machinery. In vitro experiments were performed using the ovalbumin antigen to evaluate changes in antigen-specific T cell responses.ResultsExpression of HLA-A (p<0.0001), -B (p<0.0001), -C (p<0.0001), and beta2-microglobulin (B2M, p<0.0002) was downregulated in KL tumors from TCGA, as were expression of the TAP1 (p<0.001) and TAP2 (p<0.001) transporter associated with antigen processing subunits. LKR13 KL tumors exhibited similar patterns with lower H2-k1 (p<0.0001), H2-d1 (p<0.0001), B2m (p<0.0001), Tap1 (p<0.0001) and Tap2 (p<0.0001). As a result, LKR13 KL were resistant to recognition (p<0.005) and killing (56.9% K versus 7.8% KL) by OT-I T cells. Decreased expression of IFN-gamma-regulated genes such as PSMB8 (p<0.001), PSMB9 (p<0.0001), PSMB10 (p<001), CIITA (p<0.0001), NLRC5 (p<0.0001), IFNGR1 (p<0.0001), and IFNGR2 (p<0.0001) was also noted in KL tumors. Accordingly, KL tumors were unresponsive to exogenous IFN-gamma stimulation, maintaining repression of surface H2-Kb and resistance to T cell recognition (p<0.05) and killing (12.8% K versus 4% KL). Expression of T cell chemokines and receptors CXCR3 (p<0.0001), CXCL9 (p<0.0001), and CXCL10 (p<0.0001) was also repressed, potentially contributing to the lack of T cell infiltration in KL tumors.ConclusionsKRAS-mutant tumors harboring STK11/LKB1 alterations have an immunosuppressed phenotype and resistance to PD-1/PD-L1 inhibitors. Our findings provide evidence that these alterations are associated with markedly reduced antigen presentation and resistance to T cell killing, responsiveness to IFN-gamma stimulation, and impaired production of T cell chemokines, providing mechanistic insights into this immunosuppressed phenotype that could help guide the development of new therapeutic strategies for enhancing anti-tumor immunity.

scholarly journals A New ERAP2/Iso3 Isoform Expression Is Triggered by Different Microbial Stimuli in Human Cells. Could It Play a Role in the Modulation of SARS-CoV-2 Infection?

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1951 ◽  
Author(s):  
Irma Saulle ◽  
Claudia Vanetti ◽  
Sara Goglia ◽  
Chiara Vicentini ◽  
Enrico Tombetti ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Healthy Subjects ◽  
Antigen Processing ◽  
Influenza Infection ◽  
Interferon Stimulated Genes ◽  
Mrna And Protein Expression ◽  
Cellular Immune ◽  
Antigen Processing And Presentation ◽  
Hiv 1

Following influenza infection, rs2248374-G ERAP2 expressing cells may transcribe an alternative spliced isoform: ERAP2/Iso3. This variant, unlike ERAP2-wt, is unable to trim peptides to be loaded on MHC class I molecules, but it can still dimerize with both ERAP2-wt and ERAP1-wt, thus contributing to profiling an alternative cellular immune-peptidome. In order to verify if the expression of ERAP2/Iso3 may be induced by other pathogens, PBMCs and MDMs isolated from 20 healthy subjects were stimulated with flu, LPS, CMV, HIV-AT-2, SARS-CoV-2 antigens to analyze its mRNA and protein expression. In parallel, Calu3 cell lines and PBMCs were in vitro infected with growing doses of SARS-CoV-2 (0.5, 5, 1000 MOI) and HIV-1BAL (0.1, 1, and 10 ng p24 HIV-1Bal/1 × 106 PBMCs) viruses, respectively. Results showed that: (1) ERAP2/Iso3 mRNA expression can be prompted by many pathogens and it is coupled with the modulation of several determinants (cytokines, interferon-stimulated genes, activation/inhibition markers, antigen-presentation elements) orchestrating the anti-microbial immune response (Quantigene); (2) ERAP2/Iso3 mRNA is translated into a protein (western blot); (3) ERAP2/Iso3 mRNA expression is sensitive to SARS-CoV-2 and HIV-1 concentration. Considering the key role played by ERAPs in antigen processing and presentation, it is conceivable that these enzymes may be potential targets and modulators of the pathogenicity of infectious diseases and further analyses are needed to define the role played by the different isoforms.

scholarly journals Phylogeny of Immune Recognition: Processing and Presentation of Structurally Defined Proteins in Channel Catfish Immune Responses

1991 ◽  
Vol 1 (3) ◽  
pp. 137-148 ◽  
Author(s):  
Abbe N. Vallejo ◽  
Norman W. Miller ◽  
L. William Clem
Keyword(s):  
Immune Responses ◽  
Antibody Production ◽  
Channel Catfish ◽  
Antigen Processing ◽  
Immune Recognition ◽  
Protein Antigens ◽  
Blood Leukocytes ◽  
Antigen Presenting ◽  
Antigen Processing And Presentation

This work was undertaken to investigate whether or not antigen processing and presentation are important in channel catfish in vitro secondary immune responses elicited with structurally defined proteins, namely, pigeon heart cytochrome C (pCytC), hen egg lysozyme, and horse myoglobin. The use ofin vitroantigen-pulsed and fixed B cells or monocytes as antigen presenting cells (APC) resulted in autologous peripheral blood leukocytes (PBL) responding with vigorous proliferation and antibody productionin vitro. In addition, several long-term catfish monocyte lines have been found to function as efficient APC with autologous but not allogeneic responders. Subsequent separation of the responding PBL into sIg-(T-cell-enriched) and B (sIg+) cell subsets showed that both underwent proliferative responses to antigen-pulsed and fixed APC. Moreover, allogeneic cells used as APC were found to induce only strong mixed leukocyte reactions without specificin vitroantibody production. Initial attempts at identifying the immunogenic region(s) of the protein antigens for catfish indicated there are two such regions for pCytC, namely, peptides 66-80 and 81-104.

scholarly journals Designing of cytotoxic and helper T cell epitope map provides insights into the highly contagious nature of the pandemic novel coronavirus SARS-CoV-2

2020 ◽  
Vol 7 (9) ◽  
pp. 201141 ◽  
Author(s):  
Seema Mishra
Keyword(s):  
T Cell ◽  
Antigen Processing ◽  
Cell Epitope ◽  
Computational Tools ◽  
Human Contact ◽  
Novel Coronavirus ◽  
Antigen Processing And Presentation ◽  
Clear Information ◽  
Ranked List

Novel coronavirus, SARS-CoV-2, has emerged as one of the deadliest pathogens of this century, creating an unprecedented pandemic. Belonging to the betacoronavirus family, it primarily spreads through human contact via symptomatic and asymptomatic transmission. Despite several attempts since it emerged, there is no known treatment in the form of drugs or vaccines. Hence, work on developing a potential multi-subunit vaccine is the need of the hour. In this study, attempts have been made to find globally conserved epitopes from the entire set of SARS-CoV-2 proteins as there is as yet, no clear information on the immunogenicity of these proteins. Using diverse computational tools, a ranked list of probable immunogenic, promiscuous epitopes generated through all the three main stages of antigen processing and presentation pathways has been prioritized. Moreover, several useful insights were gleaned during these analyses. One of the most important insights is that all of the proteins in this pathogen present unique epitopes, so that the targeting of a few specific viral proteins is not likely to result in an effective immune response in humans. Due to the presence of these unique epitopes in all of the SARS-CoV-2 proteins, stronger immune responses generated by T cell hyperactivation may lead to cytokine storm and immunopathology and consequently, remote chances of human survival. These epitopes, after due validation in vitro , may thus need to be presented to the human body in that form of multi-subunit epitope-based vaccine that avoids such immunopathologies.

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